One of the leading causes of morbidity resulting from neurological disorders such as spinal cord injury (SCI) is the loss of control over the lower urinary tract. SCI results in loss of voluntary control of bladder evacuation, bladder overactivity during storage (bladder hyper-reflexia) and the bladder and urethral sphincter contract simultaneously (bladder-sphincter dysynergia) instead of in a coordinated manner. Bladder-sphincter dysynergia prevents complete elimination of urine, generates high bladder pressure and requires daily urethral catheterization. These events can lead to urinary tract infections, incontinence and vesico-ureteral reflux with ensuing kidney damage. These problems result in a decreased quality of life, large medical costs and a substantial negative social and psychological impact on patients and their families. Electrical stimulation of sacral motor nerve roots can restore bladder voiding after SCI; however only when combined with the irreversible surgical transection of the sensory spinal nerve roots (i.e., a dorsal rhizotomy) to eliminate reflex contractions of the urethral sphincter that otherwise prevent voiding. Other effects of the rhizotomy (loss of remaining sensation, reflex sexual function and reflex defecation) limit the clinical acceptance of this procedure. The goal of the proposed project is to develop a neural prosthesis to restore bladder function that does not require a dorsal rhizotomy. We propose an innovative approach using afferent (sensory) stimulation that exploits the existing spinal circuitry to produce voiding. We have previously shown that electrical stimulation of sensory nerves can evoke bladder contractions and produce voiding. This project will demonstrate the feasibility of using sensory stimulation combined with motor stimulation to produce voiding. This approach would eliminate the need for a dorsal rhizotomy and, if successful, can be rapidly moved into clinical deployment. Complementary experiments will be conducted in animals and people with SCI to quantify the effectiveness of this approach and to translate animal model results to human feasibility studies. This approach to restoration of bladder voiding is expected to increase our understanding of afferent-mediated neurophysiology of the lower urinary tract and, more importantly, to increase the number of people who benefit from neuroprosthetic bladder control to improve their health and quality of life while reducing costs to the healthcare system. [unreadable] [unreadable] [unreadable]